1. RESULTS 4D-Computed Tomography Guided Treatment Planning for Intrahepatic Tumors Yen-Lin Chen, M.D. 1,2, Eike Rietzel, Ph.D. 1,2, Judith Adams 1,2, John Wolfgang, Ph.D. 1,2, Paul Busse, M.D. Ph.D. 1,2, Christopher Willett, M.D. 3, George T.Y. Chen, Ph.D. 1,2 1 Dept. of Radiation Oncology, Massachusetts General Hospital, 2 Harvard Medical School, 3 Dept. of Radiation Oncology Duke Medical Center INTRODUCTION Respiratory motion can result in significant artifacts on light breathing helical CT scans which are commonly used for 3D conformal radiation treatment planning. Because a light breathing helical CT scan captures the tumor and surrounding organ at varying phases of a respiratory cycle, radiation planning based on a single scan can potentially result in geographic miss of the tumor target volume. Traditionally, this problem has been overcome by the use of a large planning target margin which encompasses the full extent of abdominal wall or surgical clip motion anteriorly-posteriorly, laterally, and superiorly-inferiorly measured fluoroscopically. However, such large expansion of treatment volume results in unnecessary treatment of the surrounding normal tissues. In radiation treatment of unresectable intrahepatic tumors such as hepatocellular carcinoma, cholangiocarcinoma, or liver metastases, the dose to the liver is the main dose-limiting factor. 4-D CT allows modeling of the trajectory of the tumor during normal patient respiratory cycle. Such information can be incorporated into radiation planning and treatment delivery to account for intrafractional liver motion and allow for better coverage of a moving intrahepatic tumor target, tighter treatment margins, and better sparing of surrounding liver. CONCLUSIONS 4DCT provides a temporally-spatially more accurate set of data on patient anatomy during normal breathing. Respiratory induced tumor and organ motion can result in potential geographic miss and higher dose to normal liver. 4DCT allows incorporation of respiratory motion into the design of treatment aperture and potential for respiratory gating The result is better tumor coverage throughout the respiratory cycle and more accurate assessment of tumor dose and normal tissue dose. The benefit of this modeling is particularly useful in treating intrahepatic tumors where respiratory effect can be significant. Fig.5a LBCT plan appears to provide adequate coverage when DVH is calculated on LBCT (  ). However, when DVH is calculated using 4DCT, the LBCT plan only deliver the prescription dose to 90% of the tumor at inspiration (  ) and 70% at end-expiration (  ). The 4DCT plan on the other hand provides 100% coverage throughout the respiratory cycle (inspiration — and expiration - - -). Using the 4D CT, one can gate radiation delivery according to the tumor position at a particular part of the respiratory cycle. However, only when the gating is in phase does the tumor receive full coverage (- * -). When out of phase, the gated treatment results in inadequate target coverage (). Fig.5b 4DCT plan reduces liver dose when compared to the LBCT plan, while providing better CTV coverage. The gated plan delivers the lowest dose to the liver. Light breathing CT plan on a 4D- reconstructed image from end expiration Fig.3 Coronal image from light breathing helical CT for a patient with unresectable hepatocellular carcinoma treated with AP and R lateral beam arrangement. Motion artifact can be seen along the superior contour of the liver and the diaphragm. METHODS 10 patients with unresectable intrahepatic tumors (4 cholangiocarcinoma, 4 solitary liver metastasis, and 2 hepatocellular carcinoma) were scanned under an IRB-approved organ motion imaging protocol. Each patient underwent ultrasound-guided placement of 3 to 4 radio-opaque clips near the tumor periphery. Surgical clip motion was measured under fluoroscopy. A light breathing helical CT scan (LBCT) was obtained on a GE multi-slice scanner for standard 3D conformal radiation planning. A conformal 3D treatment plan based on the light breathing scan (LBCT plan) was generated using a planning target volume (PTV) defined by CTV plus the maximal range of surgical clip motion measured fluoroscopically plus 5 mm for setup uncertainty. To model the effects of respiration, 4DCT data was acquired using axial cine mode of a multi-slice CT scanner. 20-25 images were reconstructed at each couch position for a full respiratory cycle. Each image was correlated with a specific respiratory phase using the Varian RPM-system. Images were then sorted using Advantag4D software into 10 evenly spaced respiratory phases from 0 to 100% inspiration to inspiration. Tumor and liver volumes were delineated using axial image data sets from each respiratory phase. An internal target volume (ITV) was defined by the union of CTV contours from all 10 respiratory phases. A conformal plan was generated using the same beam arrangements optimized for the LBCT plan. However, instead of PTV, the 4DCT plan treated the ITV plus 5 mm uniform expansion for setup uncertainty. Lastly, a respiratory-gated plan was generated to deliver treatment during 20% of the respiratory cycle near end-expiration. Dose volume histograms for CTV and liver were generated for the following scenarios to evaluate the impact of respiration on dose distribution: 1) LBCT plan with DVH calculated on LBCT (standard treatment planning) 2) LBCT plan with DVH calculated on 4DCT (to assess true dose distribution during various respiratory cycles) 3) 4DCT plan with DVH calculated on 4DCT 4) Gated plan with DVH calculated for treatment theoretically delivered in and out of phase with respiratory cycle. Fig. 2: Liver and hepatocellular carcinoma motion seen on the same coronal slice. LBCT obtained using standard helical CT scan acquired during light breathing shows motion artifacts. Note the jagged liver and tumor edges. 4DCT reconstructions during various phases of respiration (0=end expiration 40%=near end inspiration) for the same coronal section shows significant reduction of respiration induced motion artifacts. Note the smooth liver and tumor edges. Liver volume was consistent among various respiratory phases on 4D (range 1.2 L to 1.22 L), whereas the LBCT underestimated the liver volume by 200 cc. Fig.4 Radiation treatment based on light breathing CT misses the superior portion of the tumor during full expiration (left). In comparision, the 4DCT based treatment volume covers the tumor througout respiration (right). Fig.1 Peritumoral surgical clip motion for a hepatocelluar carcinoma patient during all 10 phases of a full cycle of respiration. Most motion occurs in the superior-inferior axis (range of 1.8 cm), followed by anterior-posterior axis (range of 1 cm), and least in the right-left axis (range of 3 mm). Motion artifacts Isodose lines: 100% 90% 70% 50% 4D CT plan on a 4D-reconstructed coronal image from end expiration Light breathing CT LBCT 4DCT 0% 4DCT 20% Superior Anterior Right Superior Anterior Right Surgical clip motion during respiration Rel. liver volume [%] 5b. Comparison of liver dose volume histograms LB Plan on LBCT Undercoverage of CTV by the LB Plan at end expiration Rel. CTV volume [%] 5a. Comparison of CTV dose volume histograms